Objective. To generate phage-displayed anti-idiotypic antibody single chain variable fragments (anti - Id ScFv) to MG7 monoclonal antibody (McAb) directed against gastric carcinoma so as to lay a foundation for develo...Objective. To generate phage-displayed anti-idiotypic antibody single chain variable fragments (anti - Id ScFv) to MG7 monoclonal antibody (McAb) directed against gastric carcinoma so as to lay a foundation for developing anti-Id ScFv vaccine of the cancer.Methods. Balb/c mice were immunized i. p. with MG7 McAb conjugated with keyhole limpet hemocyanin (KLH), and mRNA was isolated from the spleens of the immunized mice. Heavy and light chain (VH and VL) genes of antibody were amplified separately and assembled into ScFv genes with a linker DNA by PCR. The ScFv genes were ligated into the phagemid vector pCANTAB5E and the ligated sample was transformed into competent E. coli TGI. The transformants were infected with M13K07 helper phage to yield recombinant phages displaying ScFv on the tips of M13 phage. After 4 rounds of panning with MG7, the MG7-positive clones were selected by ELISA from the enriched phages. The types of the anti-Id ScFv displayed on the selected phage clones were preliminarily identified by competition ELISA.Results. The VH, VL and ScFv DNAs were about 340 bp, 320 bp and 750 bp respectively. Twenty-four MG7-positive clones were selected from 60 enriched phage clones, among which 5 displayed β or γ type anti-Id ScFv.Conclusion. The anti-Id ScFv to MG7 McAb can be successfully selected by recombinant phage antibody technique, which paves a way for the study of prevention and cure of gastric carcinoma by using anti-Id ScFv.展开更多
Objective: The aim of this study was to investigate the efficacy and safety profiles of bevacizumab, the commonly used monoclonal antibody and its safety profiles were challenging, based on Chinese cancer patients. Me...Objective: The aim of this study was to investigate the efficacy and safety profiles of bevacizumab, the commonly used monoclonal antibody and its safety profiles were challenging, based on Chinese cancer patients. Methods: All the papers studied on Chinese cancer patients treated by bevacizumab were found in both databases of Chinese journal database for fulltext and PubMed were collected. The commonly used efficacy index such as disease control rate (CR + PR + SD) and response rate (CR + PR) were analyzed, and the bevacizumab related side effects were analyzed too. Results: (1) There were ten original papers contained total 199 patients who were the candidates to analyze the safety profiles, and 115 patients with colorectal cancer in five papers who were candidates to analyze the efficacy. (2) Nine in ten papers set the dose of bevacizumab in 2.5 mg/kg/week - 5 mg/kg/week, and the biweekly was the standard chemotherapy interval. (3) The disease control rate and response rate in Chinese colorectal cancer patients were 85% (95% CI: 79%-92%) and 61% (95% CI: 52%-70%), respectively. (4) The side effects related to bevacizumab were rare and most of them were grades 1-2, and only one case with grade 4 bleeding was recorded and only two cases with discontinuation of bevacizumab since hemoplysis. Also, the grades 3-4 side effects related cytotoxic agents were not common. Conclusion: This study summarized the data of Chinese cancer patients treated by bevacizumab-contained regimens, and it showed that the monoclonal antibody was effective and safe for Chinese patients as the West patients.展开更多
Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be esti...Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be estimated based on limited clinical data,leading to instability of the final model.In the present study,we analyzed the predictive ability and applicability of a simplified quasi-steady state (QSS)model with the assumption that the total target concentration was a constant parameter during treatment with monoelonal antibody in clinical data modeling.Based on the parameters of a published TMDD model of denosumab,simulations were performed at population and individual levels.Then,a simplified TMDD model,QSS model, was used to examine the effects of hypotheses,in which the total receptor concentration was constant or variable on model fit and stability of parameter estimation.Both simulations at the population level and model fit results of simulated individual data showed that at the therapeutic doses,the total receptor concentration had little influence on changes in drug concentration,and the model with constant total receptor concentration had the same predictive power.The validated hypothesis could be applied to clinical trial design and selection of the optimal PK model in the development of monoclonal antibodies.展开更多
基金This work was supported by the National Natural Sciences Founda- tion of China(NSFC, No. 39800057, No. 30200338) the National "863" High-tech Project Foundation (No. 102-10-01 -06) +1 种基金National Distinguished Youth Program of NSFC(No. 39525020) This wor
文摘Objective. To generate phage-displayed anti-idiotypic antibody single chain variable fragments (anti - Id ScFv) to MG7 monoclonal antibody (McAb) directed against gastric carcinoma so as to lay a foundation for developing anti-Id ScFv vaccine of the cancer.Methods. Balb/c mice were immunized i. p. with MG7 McAb conjugated with keyhole limpet hemocyanin (KLH), and mRNA was isolated from the spleens of the immunized mice. Heavy and light chain (VH and VL) genes of antibody were amplified separately and assembled into ScFv genes with a linker DNA by PCR. The ScFv genes were ligated into the phagemid vector pCANTAB5E and the ligated sample was transformed into competent E. coli TGI. The transformants were infected with M13K07 helper phage to yield recombinant phages displaying ScFv on the tips of M13 phage. After 4 rounds of panning with MG7, the MG7-positive clones were selected by ELISA from the enriched phages. The types of the anti-Id ScFv displayed on the selected phage clones were preliminarily identified by competition ELISA.Results. The VH, VL and ScFv DNAs were about 340 bp, 320 bp and 750 bp respectively. Twenty-four MG7-positive clones were selected from 60 enriched phage clones, among which 5 displayed β or γ type anti-Id ScFv.Conclusion. The anti-Id ScFv to MG7 McAb can be successfully selected by recombinant phage antibody technique, which paves a way for the study of prevention and cure of gastric carcinoma by using anti-Id ScFv.
文摘Objective: The aim of this study was to investigate the efficacy and safety profiles of bevacizumab, the commonly used monoclonal antibody and its safety profiles were challenging, based on Chinese cancer patients. Methods: All the papers studied on Chinese cancer patients treated by bevacizumab were found in both databases of Chinese journal database for fulltext and PubMed were collected. The commonly used efficacy index such as disease control rate (CR + PR + SD) and response rate (CR + PR) were analyzed, and the bevacizumab related side effects were analyzed too. Results: (1) There were ten original papers contained total 199 patients who were the candidates to analyze the safety profiles, and 115 patients with colorectal cancer in five papers who were candidates to analyze the efficacy. (2) Nine in ten papers set the dose of bevacizumab in 2.5 mg/kg/week - 5 mg/kg/week, and the biweekly was the standard chemotherapy interval. (3) The disease control rate and response rate in Chinese colorectal cancer patients were 85% (95% CI: 79%-92%) and 61% (95% CI: 52%-70%), respectively. (4) The side effects related to bevacizumab were rare and most of them were grades 1-2, and only one case with grade 4 bleeding was recorded and only two cases with discontinuation of bevacizumab since hemoplysis. Also, the grades 3-4 side effects related cytotoxic agents were not common. Conclusion: This study summarized the data of Chinese cancer patients treated by bevacizumab-contained regimens, and it showed that the monoclonal antibody was effective and safe for Chinese patients as the West patients.
文摘Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be estimated based on limited clinical data,leading to instability of the final model.In the present study,we analyzed the predictive ability and applicability of a simplified quasi-steady state (QSS)model with the assumption that the total target concentration was a constant parameter during treatment with monoelonal antibody in clinical data modeling.Based on the parameters of a published TMDD model of denosumab,simulations were performed at population and individual levels.Then,a simplified TMDD model,QSS model, was used to examine the effects of hypotheses,in which the total receptor concentration was constant or variable on model fit and stability of parameter estimation.Both simulations at the population level and model fit results of simulated individual data showed that at the therapeutic doses,the total receptor concentration had little influence on changes in drug concentration,and the model with constant total receptor concentration had the same predictive power.The validated hypothesis could be applied to clinical trial design and selection of the optimal PK model in the development of monoclonal antibodies.
